Chronic therapy with immunosupressive drugs has been associated with an increased occurrence of neoplastic disease in certain clinical situations. Selected patients with SLE and other inflammatory diseases of connective tissue are currently receiving therapy with cyclophosphamide, a potent suppressor of immune responsiveness. Clinical experience and therapeutic studies employing NZB/NZW mice have shown that cyclophosphamide therapy is associated with an increased incidence of neoplasms in the host with autoimmune disease. Many of these tumors were lymphomas. This information suggests that prolonged therapy of autoimmune disease with cyclophosphamide may predispose to the development of lymphoreticular tumors. Investigative efforts in this laboratory produced evidence that therapy with hydrocortisone, an anti-inflammatory drug, prolonged lifespan in NZB/NZW mice. An unexpected finding was the high incidence of sarcomas in aged hydrocortisone-treated mice. The increased incidence of neoplastic lesions in cyclophosphamide-treated mice provided an opportunity to study lymphoma development in NZB/NZW mice. Some lymphomas suppressed ANA responses in terminal sera. Cells from those tumors have been stored and frozen, and future studies will permit the Principal Investigator to characterize the properties of "suppressor" lymphoma cells. BIBLIOGRAPHIC REFERENCE: Walker, S.E., and Bole, G.G., Jr.: Selective Suppression of Autoantibody Responses in NZB/NZW Mice Treated with Long-Term Cyclophosphamide. Arthritis Rheum. 17:265-272, 1975.